Pharmacologic activation of p53 by small-molecule MDM2 antagonists

Curr Pharm Des. 2011;17(6):560-8. doi: 10.2174/138161211795222603.

Abstract

Restoring p53 activity by inhibiting the interaction between p53 and MDM2 represents an attractive approach for cancer therapy. To this end, a number of small-molecule p53-MDM2 binding inhibitors have been developed during the past several years. Nutlin-3 is a potent and selective small-molecule MDM2 antagonist that has shown considerable promise in pre-clinical studies. This review will highlight recent advances in the development of small-molecule MDM2 antagonists as potential cancer therapeutics, with special emphasis on Nutlin-3.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Genes, p53*
  • Humans
  • Imidazoles / pharmacology*
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Piperazines / pharmacology*
  • Protein Binding
  • Proto-Oncogene Proteins c-mdm2 / antagonists & inhibitors*
  • Tumor Suppressor Protein p53 / agonists*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Antineoplastic Agents
  • Imidazoles
  • Piperazines
  • Tumor Suppressor Protein p53
  • nutlin 3
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2